The article explored the mechanism of CNR1 on the malignant progression of osteosarcoma cells.The changes of high and low CNR1 expression and long-term survival in tumor tissues were analyzed by bio-analysis;CNR1 overexpression lentivirus was used to infect osteosarcoma cells;CCK-8,scratch assay,clonogenic assay,Transwell cell invasion assay and flow apoptosis assay were used to detect the changes of osteosarcoma cells'proliferation,colony formation and invasion ability,as well as the level of apoptosis;transmission electron micros-copy was used,MitoSOX probe and immunoblotting to detect changes in mitochondrial morphology and function;and nude mice loaded tumor assay to verify the growth of CNR1 high-expression osteosarcoma cells in vivo.The results showed that CNR1 expression was up-regulated in osteosarcoma tissues,and the long-term survival rate of patients in the group with high CNR1 expression was significantly higher than that in the group with low CNR1 ex-pression;the immunoblotting confirmed that lentivirus infection successfully induced the high CNR1 expression in osteosarcoma cell lines;the high expression of CNR1 significantly inhibited osteosarcoma cells'proliferation,col-ony formation,and invasive ability and induced osteosarcoma cells'apoptosis;CNR1 activated FIS1 thereby caus-ing excessive mitochondrial cleavage and inducing mitochondrial pathway apoptosis;in tumor-bearing nude mice,CNR1 overexpression inhibited malignant progression of osteosarcoma cells by promoting mitochondrial pathway apoptosis.